Synthesis and evaluation of aliphatic-chain hydroxamates capped with osthole derivatives as histone deacetylase inhibitors

Wei Jan Huang, Ching Chow Chen, Shi Wei Chao, Chia Chun Yu, Chen Yui Yang, Jih Hwa Guh, Yun Chieh Lin, Chiao I. Kuo, Ping Yang, Chung I. Chang

研究成果: 雜誌貢獻文章

26 引文 斯高帕斯(Scopus)

摘要

Our previous studies have demonstrated that osthole, a Chinese herbal compound, could be incorporated into the hydroxycinnamide scaffold of LBH-589, a potent HDAC inhibitor, as an effective hydrophobic cap; the resulting compounds showed significant potency against several HDAC isoforms. Here, we presented a series of osthole derivatives fused with the aliphatic-hydroxamate core of suberoylanilide hydroxamic acid (SAHA), a clinically-approved HDAC inhibitor. Several compounds showed potent activity against nuclear HDACs. Further assays against individual HDAC isoforms revealed that some compounds showed not only SAHA-like activity towards HDAC1, -4 and -6, they inhibited HDAC8 by log difference than SAHA and thus exhibited a broader HDAC inhibition spectrum. Among them, compound 6g showed potent antiproliferative effect on several human cancer cell lines.

原文英語
頁(從 - 到)4042-4049
頁數8
期刊European Journal of Medicinal Chemistry
46
發行號9
DOIs
出版狀態已發佈 - 九月 2011

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

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